BACKGROUND: Percutaneous rhizotomy of the Gasserian ganglion is a well-established intervention for patients suffering from refractory trigeminal pain, not amenable to pharmacological management or microvascular decompression. Traditionally conducted under fluoroscopic guidance using Hartel's technique, this study investigates a modified approach employing low-dose CT guidance to achieve maximal procedural precision and safety with the emphasis on minimizing radiation exposure. METHODS: A retrospective analysis of patients undergoing percutaneous rhizotomy of the Gasserian ganglion at our institution was undertaken. Procedures were divided into fluoroscopy and CT-guided foramen ovale (FO) cannulation cohorts. Radiation doses were assessed, excluding cases with incomplete data. The study included 32 procedures in the fluoroscopy group and 30 in the CT group. RESULTS: In the CT-guided group, the median effective dose was 0.21 mSv. The median number of CT scans per procedure was 4.5, and the median procedure time was 15 min. Successful FO cannulation was achieved in all 30 procedures (100%). In the fluoroscopy group, the median effective dose was 0.022 mSv, and the median procedure time was 15 min. Cannulation of FO was successful in 31 of 32 procedures (96.9%). The only complications in the CT-guided group were three minor cheek hematomas. Immediate pain relief in the CT-guided group was reported in 25 of 30 procedures (83.3%), 22 of 30 (73.3%) provided relief at one month, and 10 of 18 (55.6%) procedures resulting in pain relief at one month continued to provide relief after two years. CONCLUSION: Low-dose CT-guided percutaneous rhizotomy conducted in the radiology suite carries negligible radiation exposure for patients and eliminates it for personnel. This method is fast, simple, precise, and carries a very low risk of complications.
- MeSH
- dávka záření MeSH
- dospělí MeSH
- fluoroskopie metody MeSH
- ganglion trigeminale chirurgie diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuralgie trigeminu * chirurgie diagnostické zobrazování radioterapie MeSH
- počítačová rentgenová tomografie * metody MeSH
- radiační expozice * prevence a kontrola MeSH
- retrospektivní studie MeSH
- rizotomie * metody MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Our understanding of how the mammalian somatosensory system detects noxious cold is still limited. While the role of TRPM8 in signaling mild non-noxious coolness is reasonably understood, the molecular identity of channels transducing painful cold stimuli remains unresolved. TRPC5 was originally described to contribute to moderate cold responses of dorsal root ganglia neurons in vitro, but mice lacking TRPC5 exhibited no change in behavioral responses to cold temperature. The question of why a channel endowed with the ability to be activated by cooling contributes to the cold response only under certain conditions is currently being intensively studied. It seems increasingly likely that the physiological detection of cold temperatures involves multiple different channels and mechanisms that modulate the threshold and intensity of perception. In this review, we aim to outline how TRPC5 may contribute to these mechanisms and what molecular features are important for its role as a cold sensor.
- MeSH
- kationtové kanály TRPC * metabolismus MeSH
- kationtové kanály TRPM metabolismus MeSH
- lidé MeSH
- myši MeSH
- nízká teplota * MeSH
- spinální ganglia metabolismus fyziologie MeSH
- vnímání teploty * fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.
- MeSH
- adenosintrifosfát metabolismus farmakologie MeSH
- krysa rodu rattus MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus farmakologie MeSH
- neuroglie metabolismus MeSH
- NF-kappa B * metabolismus MeSH
- novorozená zvířata MeSH
- potkani Sprague-Dawley MeSH
- purinergní receptory P2X4 * genetika metabolismus MeSH
- spinální ganglia metabolismus MeSH
- vápník metabolismus farmakologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1 (α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by α9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration.SIGNIFICANCE STATEMENT Restoration of neurologic function after spinal cord injury has yet to be achieved in human patients. To accomplish this, severed nerve fibers must be made to regenerate. Reconstruction of nerve pathways has not been possible, but recently, a method for stimulating long-distance axon regeneration of sensory fibers in rodents has been developed. This research uses profiling of messenger RNAs in the regenerating sensory neurons to discover which mechanisms are activated. This study shows that the regenerating neurons initiate a novel CNS regeneration program which includes molecular transport, autophagy, ubiquitination, and modulation of the endoplasmic reticulum (ER). The study identifies mechanisms that neurons need to activate to regenerate their nerve fibers.
- MeSH
- axony * fyziologie MeSH
- integriny metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mícha metabolismus MeSH
- nervové receptory fyziologie MeSH
- poranění míchy * terapie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- regenerace nervu fyziologie MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Different types of spiral ganglion neurons (SGNs) are essential for auditory perception by transmitting complex auditory information from hair cells (HCs) to the brain. Here, we use deep, single cell transcriptomics to study the molecular mechanisms that govern their identity and organization in mice. We identify a core set of temporally patterned genes and gene regulatory networks that may contribute to the diversification of SGNs through sequential binary decisions and demonstrate a role for NEUROD1 in driving specification of a Ic-SGN phenotype. We also find that each trajectory of the decision tree is defined by initial co-expression of alternative subtype molecular controls followed by gradual shifts toward cell fate resolution. Finally, analysis of both developing SGN and HC types reveals cell-cell signaling potentially playing a role in the differentiation of SGNs. Our results indicate that SGN identities are drafted prior to birth and reveal molecular principles that shape their differentiation and will facilitate studies of their development, physiology, and dysfunction.
- MeSH
- buněčná diferenciace genetika MeSH
- ganglion spirale * MeSH
- myši MeSH
- neurony * metabolismus MeSH
- RNA metabolismus MeSH
- vláskové buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Vagal afferents regulate numerous physiological functions including arterial blood pressure, heart rate, breathing, and nociception. Cell bodies of vagal afferents reside in the inferior vagal (nodose) ganglia and their stimulation by various means is being considered as a way to regulate cardiorespiratory responses and control pain sensations. Stimulation of the nodose by exposure to infrared light is recently being considered as a precise way to elicit responses. These responses would likely involve the activity of temperature-sensitive membrane-bound channels. While papers have been published to track the expression of these transient receptor potential ion channels (TRPs), further studies are warranted to determine the in situ expression of the endogenous TRP proteins in the nodose ganglia to fully understand their pattern of expression, subcellular locations, and functions in this animal model. TRP ion channels are a superfamily of Na+ /Ca2+ -channels whose members are temperature- and/or mechano-sensitive and therefore represent a potential set of proteins that will be activated directly or indirectly by infrared light. Here, we report the spatial localization of six TRP channels, TRPV1, TRPV4, TRPM3, TRPM8, TRPA1, and TRPC1, from nodose ganglia taken from juvenile male Sprague-Dawley rats. The channels were detected using immunohistology with fluorescent tags on cryosections and imaged using confocal microscopy. All six TRP channels were detected with different levels of intensity in neuronal cell bodies and some were also detected in axonal fibers and blood vessels. The TRP receptors differed in their prevalence, in their patterns of expression, and in subcellular expression/localization. More specifically, TRPV1, TRPV4, TRPA1, TRPM8, TRPC1, and TRPM3 were found in vagal afferent cell bodies with a wide range of immunostaining intensity from neuron to neuron. Immunostaining for TRPV1, TRPV4, and TRPA1 appeared as fine particles scattered throughout the cytoplasm of the cell body. Intense TRPV1 immunostaining was also evident in a subset of axonal fibers. TRPM8 and TRPC1 were expressed in courser particles suggesting different subcellular compartments than for TRPV1. The localization of TRPM3 differed markedly from the other TRP channels with an immunostaining pattern that was localized to the periphery of a subset of cell bodies, whereas a scattering or no immunostaining was detected within the bulk of the cytoplasm. TRPV4 and TRPC1 were also expressed on the walls of blood vessels. The finding that all six TRP channels (representing four subfamilies) were present in the nodose ganglia provides the basis for studies designed to understand the roles of these channels in sensory transmission within vagal afferent fibers and in the responses elicited by exposure of nodose ganglia to infrared light and other stimuli. Depending on the location and functionality of the TRP channels, they may regulate the flux of Na+ /Ca2+ -across the membranes of cell bodies and axons of sensory afferents, efferent (motor) fibers coursing through the ganglia, and in vascular smooth muscle.
- MeSH
- ganglion inferius metabolismus MeSH
- kationtové kanály TRP * metabolismus MeSH
- kationtové kanály TRPM * metabolismus MeSH
- kationtové kanály TRPV MeSH
- krysa rodu rattus MeSH
- nervus vagus metabolismus MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Nucleolin is a multifunctional RNA Binding Protein (RBP) with diverse subcellular localizations, including the nucleolus in all eukaryotic cells, the plasma membrane in tumor cells, and the axon in neurons. Here we show that the glycine arginine rich (GAR) domain of nucleolin drives subcellular localization via protein-protein interactions with a kinesin light chain. In addition, GAR sequences mediate plasma membrane interactions of nucleolin. Both these modalities are in addition to the already reported involvement of the GAR domain in liquid-liquid phase separation in the nucleolus. Nucleolin transport to axons requires the GAR domain, and heterozygous GAR deletion mice reveal reduced axonal localization of nucleolin cargo mRNAs and enhanced sensory neuron growth. Thus, the GAR domain governs axonal transport of a growth controlling RNA-RBP complex in neurons, and is a versatile localization determinant for different subcellular compartments. Localization determination by GAR domains may explain why GAR mutants in diverse RBPs are associated with neurodegenerative disease.
- MeSH
- axonální transport genetika MeSH
- buněčné jadérko metabolismus ultrastruktura MeSH
- exprese genu MeSH
- fosfoproteiny chemie genetika metabolismus MeSH
- HEK293 buňky MeSH
- HeLa buňky MeSH
- kineziny genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mutace MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nervus ischiadicus cytologie metabolismus MeSH
- neurony cytologie metabolismus MeSH
- primární buněčná kultura MeSH
- proteinové domény MeSH
- proteiny vázající RNA chemie genetika metabolismus MeSH
- sekvence aminokyselin MeSH
- spinální ganglia cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Chronic pain is regarded to be one of the common and refractory diseases to cure in the clinic. One hundred Hz electroacupuncture (EA) is commonly used for inflammatory pain and 2 Hz for neuropathic pain possibly by modulating the transient receptor potential vanilloid subtype 1 (TRPV1) or the purinergic P2X3 related pathways. To clarify the mechanism of EA under various conditions of pathological pain, rats received a subcutaneous administration of complete Freund's adjuvant (CFA) for inflammatory pain and spared nerve injury (SNI) for neuropathic pain. The EA was performed at the bilateral ST36 and BL60 1 d after CFA or SNI being successfully established for 3 consecutive days. The mechanical hyperalgesia test was measured at baseline, 1 d after model establishment, 1 d and 3 d after EA. The co-expression changes, co-immunoprecipitation of TRPV1 and P2X3, and spontaneous pain behaviors (SPB) test were performed 3 d after EA stimulation. One hundred Hz EA or 2Hz EA stimulation could effectively down-regulate the hyperalgesia of CFA or SNI rats. The increased co-expression ratio between TRPV1 and P2X3 at the dorsal root ganglion (DRG) in two types of pain could be reduced by 100Hz or 2Hz EA intervention. While 100Hz or 2Hz EA was not able to eliminate the direct physical interaction between TRPV1 and P2X3. Moreover, EA could significantly inhibit the SPB induced by the co-activation of peripheral TRPV1 and P2X3. All results indicated that EA could significantly reduce the hyperalgesia and the SPB, which was partly related to inhibiting the co-expression and indirect interaction between peripheral TRPV1 and P2X3.
- MeSH
- elektroakupunktura * MeSH
- hyperalgezie metabolismus patofyziologie terapie MeSH
- kationtové kanály TRPV metabolismus MeSH
- modely nemocí na zvířatech MeSH
- neuralgie metabolismus patofyziologie terapie MeSH
- potkani Sprague-Dawley MeSH
- práh bolesti MeSH
- purinergní receptory P2X3 metabolismus MeSH
- signální transdukce MeSH
- spinální ganglia metabolismus patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
In this brief report, we demonstrate that the Cav3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Cav3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Cav3.3 compared to controls using Western blot analysis of whole trigeminal ganglia tissues. Finally, we demonstrated that intraperitoneal injection of a selective TAT-based Cav3.3 blocking peptide in FRICT-ION mice significantly reduces Cav3.3 protein expression at the peak anti-allodynic effect (4 hrs post-injection) of the attenuated neuropathic pain behavior. We also suggest that blockade of Cav3.3 may be more effective in attenuating trigeminal neuropathic pain in female than male FRICT-ION mice. Therefore, blocking or attenuating Cav3.3 function may be an effective strategy for the treatment of trigeminal neuropathic pain.
This review provides an up-to-date source of information on the primary auditory neurons or spiral ganglion neurons in the cochlea. These neurons transmit auditory information in the form of electric signals from sensory hair cells to the first auditory nuclei of the brain stem, the cochlear nuclei. Congenital and acquired neurosensory hearing loss affects millions of people worldwide. An increasing body of evidence suggest that the primary auditory neurons degenerate due to noise exposure and aging more readily than sensory cells, and thus, auditory neurons are a primary target for regenerative therapy. A better understanding of the development and function of these neurons is the ultimate goal for long-term maintenance, regeneration, and stem cell replacement therapy. In this review, we provide an overview of the key molecular factors responsible for the function and neurogenesis of the primary auditory neurons, as well as a brief introduction to stem cell research focused on the replacement and generation of auditory neurons.
- MeSH
- ganglion spirale embryologie fyziologie MeSH
- indukované pluripotentní kmenové buňky cytologie MeSH
- kochlea embryologie fyziologie MeSH
- lidé MeSH
- mozkový kmen MeSH
- mutace MeSH
- myši MeSH
- neurogeneze MeSH
- neurony fyziologie MeSH
- nucleus cochlearis embryologie fyziologie MeSH
- percepční nedoslýchavost patofyziologie MeSH
- regenerativní lékařství metody MeSH
- sekvence nukleotidů MeSH
- sluchové kmenové evokované potenciály MeSH
- vláskové buňky fyziologie MeSH
- vnitřní ucho embryologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
